PROJECT TITLE: A Two-Year Prospective Longitudinal Study using Quantitative and Qualitative Assessments to Define the Natural History of Gastrointestinal Symptoms in Patients with Parkinson’s Disease or at Risk for Developing the Motor Symptoms of Parkinson’s Disease

Objective: To characterize the natural progression of gastrointestinal symptoms in patients with Parkinson’s disease, or who are at high risk for developing the motor symptoms of Parkinson’s disease, using the Gastrointestinal Symptom Relief Scale (GSRS) and Gastroparesis Cardinal Symptom Index (GCSI); high resolution esophageal manometry to evaluate the functioning of the esophageal muscle and sphincters; high resolution anorectal manometry to evaluate anorectal motility and coordination; and the SmartPill® to measure gastric, colon, and small bowel transit times.

Background: Parkinson’s disease results in progressive accumulation of alpha-synuclein in the neurons of the gastrointestinal tract, resulting in dysfunction and ultimately degeneration of neurons in the gastrointestinal tract which leads to clinically important symptoms that can be quantified and measured over time. Quantitative assessments using newly developed high resolution esophageal and anorectal manometry, and the SmartPill® device may be more sensitive at quantifying gastrointestinal symptoms and may be better endpoints for clinical studies designed for drug approvals than symptom based assessments in Parkinson’s disease.

Methods/Design: This is a single center, prospective, non-interventional, cross-sectional and longitudinal study of the natural history of gastrointestinal symptoms associated with Parkinson’s disease. Data from this study will be used to characterize the progression of gastrointestinal symptoms associated with Parkinson’s disease and determine which outcome measures will be best to assess the efficacy of future potential therapies and to optimize ongoing patient management.

Relevance to Diagnosis/Treatment of Parkinson’s disease: Quantitative assessments may be able to demonstrate improvement or worsening of gastrointestinal dysfunction in relation to changes in medication and therefore be better for diagnosis of gastrointestinal issues and for following response to treatment. Analysis of the gastrointestinal tract may also lead to earlier diagnosis of Parkinson’s disease, quicker referral to specialty centers and improved patient care and patient outcomes.

September 2017 Project Update:

This project is ongoing and in 2017 we presented the first set of data on the esophageal findings at the Movement Disorder Meeting in Portland by Dr. Salima Brillman. The Parkinson Alliance/Parkinson’s Unity Walk was acknowledged on the poster. Dysphagia is common in PD; its etiology multifactorial and its management challenging. In a retrospective cohort analysis, we aimed to objectively characterize dysphagia and/or other esophageal symptoms in PD, assess the prevalence of outflow obstruction, disorders of esophageal peristalsis leading to impaired esophageal clearance and highlight objective parameters that can help in current management. In a prospective cohort of PD patients, we evaluated the intrapersonal variability of these esophageal motility findings in patients with various disease stages and with or without esophageal symptoms.

95 patients with PD formed the first cohort of the study. Of the 95, 33 with symptoms were studied with high-resolution manometry (HRM) with the other 62 were excluded from HRM. The 62 were further classified 34 as having no symptoms and 28 as having either gastroesophageal reflux disease (GERD) -6, oropharyngeal dysphagia (OD) -8 and 14 patients unwilling to be further examined.

The conclusions from the first phase of this work indicate that dysphagia is common in PD and is associated with a high prevalence of underlying motility disturbances as identified by HRM. The exact impact of these motility abnormalities on symptom induction, their variability over time in the same patient, their evolution as well as their role influencing motor fluctuations and clinical management are still unclear and will be provided with our prospective study and validation.

In addition, we recently had another paper accepted entitled, “Pilot cohort study of endoscopic botulinum neurotoxin injection in Parkinson’s Disease” George Triadafilopoulos, MD, Rita Gandhy, MD, Carrolee Barlow, MD, PhD. which describes our work using Botox to treat the complications of enteric nervous system dysfunction in Parkinson’s.